In Vivo Evaluation of the Role of Neutrophil-Derived Free Radicals in the Development of Endotoxic Shock
Clinical and experimental data strongly suggests that a significant portion of the peripheral responses occurring during septic shock are initiated by endotoxin.1 One of the peripheral responses initiated by endotoxin is the stimulation of neutrophils resulting from interaction with tumor necrosis factor derived from endotoxin activated macrophages. Stimulated neutrophils have the potential to marginate along endothelial cells and migrate to extravascular tissue. Once this has occurred activated neutrophils have the capacity to release enzymes, hypochlorous acid, and importantly hydrogen peroxide and superoxide ions resulting in cellular injury. Tumor necrosis factor is becoming increasingly recognized as a major mediator of sepsis and the effects of endotoxin. Evidence strongly suggests that a majority of tumor necrosis factor effects are a result of its action on neutrophils and oxidative metabolism.2 Endotoxin has a dual action on neutrophil function since, in addition to the tumor necrosis factor mediated effect, this toxin has been shown to prime neutrophils for an enhanced oxidative burst and release of neutrophil-generated mediators of injury.3 This study was designed to determine the significance of neutrophils in the development of endotoxic shock by challenging neutropenic rats with endotoxin.
KeywordsCentral Venous Pressure Hypochlorous Acid Endotoxic Shock Hypotensive Episode Inadequate Tissue Perfusion